Vaccine to help smokers quit is a long way off

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Behind the Headlines

Thursday June 28 2012

DNA anti-nicotine stop smoking vaccine is a long way off

A “DNA vaccine will halt nicotine cravings and could even be used to stop children starting the habit”, the Daily Mail today reported. The paper added: “Just one jab could provide lifelong protection against nicotine cravings.”

This story is based on research in mice. It examined the effects of a newly devised injection that transferred the gene responsible for producing antibodies that target nicotine into the mice. Researchers gave these mice, which were primed with the antibodies, a dose of nicotine. They examined the effects of this upon nicotine levels in the mice’s brain and blood. They also did the same to mice that had not been given the gene transfer.

The researchers found that the mice which had been given the jab had significantly reduced levels of nicotine in their brains compared with mice that were not given the jab. They concluded that this injection led to a reduction in nicotine exposure in the brains of treated mice. Further research is needed to see if it would work as well in people.

This study suggests that it may be possible to develop a “smoking vaccine”, but it is a long way off. It is difficult to tell yet whether the vaccination would be safe and effective, or who would be eligible for it. It is also unclear whether reducing the brain’s exposure to nicotine would help people to stop smoking, or prevent them starting in the first place. It’s important to remember that finding smoking hard to quit may not be due solely to nicotine addiction alone.

Where did the story come from?

The study was carried out by researchers from Cornell University and the Scripps Research Institute in the US and was funded by the US National Institutes of Health and the Tobacco-Related Disease Research Programme.

The study was published in the peer-reviewed journal Science Translational Medicine.

The media largely covered this study appropriately, despite headlines implying that the study was conducted in humans. In their stories, the Daily Mail and the BBC both pointed out that the study was conducted in mice, that the findings may not carry over to human studies and that it is likely to be years before a jab could be available. Both also did well to mention the potential ethical implications of gene therapy for an addiction that has both physical and psychological components.

What kind of research was this?

This was an animal study. It examined the impact of an injection that affects how the body handles and responds to nicotine. The injection involved the transfer of a gene that produces a type of protein called an antibody. The antibody targets nicotine, binding to it and preventing it from entering the brain. In order for antibodies to target the nicotine before it gets to the brain, they have to be continuously present in the blood in sufficient levels.

Animal studies are often used early in the research process to determine whether the theory underlying it is sound. Once confirmed, the research can move on to testing people. However, the results seen in animal studies do not always hold in people. As such, optimistic findings from these early studies may ultimately not work for us. This makes it difficult to determine whether or not a “smoking jab” is really on its way.

What did the research involve?

The researchers developed an injection that would lead to the transfer of a gene into the DNA of a group of mice. Once integrated with the mouse genome, this gene would begin producing an antibody that targets nicotine and binds to it. The researchers were interested to know whether the antibodies could be produced in levels high enough to effectively recognise and bind to nicotine over a long time. To assess this, they gave a group of mice three different doses of the injection, and measured the antibody levels (or titres) over time.

They then assessed how the injection affected nicotine levels in the mice’s brain compared with the levels in their blood. The researchers thought that the antibodies would bind to the nicotine in the blood, preventing it from reaching the brain (therefore the levels of nicotine in the blood would remain high). They injected one group of mice and left one group untreated. They then injected all of the mice with a dose of nicotine, and compared the levels of the drug present in the brain and the blood of the two groups of mice.

What were the basic results?

The researchers found that mice given the jab maintained a high level of the anti-nicotine antibody over time, with antibody titre levels the highest for the longest in mice given the highest dose. The levels in the highest group remained stable up to 18 weeks.

When assessing the affect of the injection on nicotine levels, the researchers found that the treated mice did have approximately seven times more nicotine in their blood than the untreated mice. The treated mice also had 85% lower concentration of nicotine in their brains, compared with the untreated mice. Together, these results indicate that the jab was able to produce the anti-nicotine antibodies, which then bound to the nicotine and prevented it from entering the brain, as the researchers had anticipated.

How did the researchers interpret the results?

The researchers concluded that a single injection led to consistently high anti-nicotine antibody levels, and that this prevented the drug from reaching the brain. They said that if these findings are confirmed in people, the gene transfer could be an effective therapy for preventing nicotine addiction.

Conclusion

This research has shown that gene transfer therapy can interfere with the way nicotine goes from the blood to the brain. This animal study does not, however, tell us whether an injection can stop people from taking up smoking or help them to quit.

Interpreting the results of animal research is difficult and generalising the findings to humans should be done cautiously. The researchers want to do more animal studies that would attempt to mimic nicotine addiction in humans. They said that the mice used in the current study had not been exposed to nicotine previously, and they are planning further studies in which nicotine-addicted mice are able to access the drug at will. This, the researchers suggested, is a model for smoking cigarettes and could give clues as to whether reducing the amount of nicotine in the brain is likely to alter nicotine-seeking behaviours. However, in reality this is still not the same as people smoking cigarettes.

The researchers said that current programmes to help smokers kick the habit are mostly ineffective, with the majority of smokers starting again within six months. They said that an anti-nicotine vaccine offers “a unique opportunity to address a great societal problem”.

It is important to note that smoking is not purely driven by an addiction to nicotine. Therefore, interrupting exposure to the drug may not be sufficient as this wouldn’t address the behavioural habits and psychological addiction to smoking.